What are the implications of acetaminophen (paracetamol) toxicity?

From the Guidelines

Acetaminophen toxicity can lead to severe liver injury and death, and prompt treatment with N-acetylcysteine (NAC) is essential.

Implications of Acetaminophen Toxicity

• Acetaminophen hepatotoxicity is a dose-related toxin, with most ingestions leading to acute liver failure (ALF) exceeding 10 gm/day, but severe liver injury can occur with doses as low as 3-4 gm/day 1
• The standard acetaminophen toxicity nomogram may aid in determining the likelihood of serious liver damage, but cannot be used to exclude possible toxicity due to multiple doses over time, or altered metabolism in the alcoholic or fasting patient 1
• Very high aminotransferases may be seen, with serum levels exceeding 3,500 IU/L highly correlated with acetaminophen poisoning 1

Treatment and Management

• NAC is recommended in any case of ALF in which acetaminophen overdose is a suspected or possible cause, and should be given as early as possible, but may still be of value 48 hours or more after ingestion 1
• NAC may be given orally (140 mg/kg by mouth or nasogastric tube diluted to 5% solution, followed by 70 mg/kg by mouth q 4 h 17 doses) or intravenously (loading dose is 150 mg/kg in 5% dextrose over 15 minutes; maintenance dose is 50 mg/kg given over 4 hours followed by 100 mg/kg administered over 16 hours) 1
• Activated charcoal may be useful for gastrointestinal decontamination if given within 1-4 hours of ingestion, and does not reduce the effect of NAC if administered prior to NAC 1

Prevention and Safety

• Patients should be advised to limit daily acetaminophen intake to a maximum of 4 g, and the FDA imposes a limit of 325 mg of acetaminophen per tablet, capsule, or other dosage unit in prescription products to reduce the risk of severe liver injury from acetaminophen overdosing 1
• Providers should consider limiting chronic administration of acetaminophen to 3 g or less per day due to concerns of hepatic toxicity 1

From the FDA Drug Label

Warnings Liver warning This product contains acetaminophen Severe liver damage may occur if: an adult takes more than 6 doses in 24 hours, or greater than 4000 mg of acetaminophen, the maximum daily amount a child takes more than 5 doses in 24 hours taken with other drugs containing acetaminophen taken with 3 or more alcoholic drinks every day while using this product Overdose warning Taking more than the recommended dose (overdose) may cause liver damage. In case of overdose, get medical help or contact a Poison Control Center right away. (1-800-222-1222). Quick medical attention is critical for adults as well as children even if you do not notice any signs or symptoms.

The implications of acetaminophen (paracetamol) toxicity include severe liver damage. This can occur if the recommended dose is exceeded, such as:

• Taking more than 6 doses in 24 hours as an adult
• Taking more than 5 doses in 24 hours as a child
• Taking with other drugs containing acetaminophen
• Taking with 3 or more alcoholic drinks every day In case of overdose, quick medical attention is critical to prevent liver damage 2.

From the Research

Implications of Acetaminophen (Paracetamol) Toxicity

The implications of acetaminophen (paracetamol) toxicity are severe and can be life-threatening. Some of the key implications include:

• Hepatotoxicity: Acetaminophen overdose can cause dose-dependent hepatotoxicity, leading to liver injury and even liver failure 3, 4, 5.
• Liver damage: Paracetamol toxicity can cause temporary liver dysfunction or even irreversible liver failure, requiring liver transplantation as the only therapeutic possibility 4, 5.
• Kidney damage: The toxic effects of paracetamol can also occur in the kidneys, leading to impaired phosphate and lactate turnover 4.
• Cardiac effects: Acetaminophen overdose can also lead to cardiac effects, including myocardial infarction, heart dysfunction and failure, cardiac arrhythmias, pericarditis, and sudden cardiac death 6.
• Mortality: Despite the use of antidotes like acetylcysteine, paracetamol overdose can still result in significant mortality, with estimates suggesting that it is involved in 6% of poisonings, 56% of severe acute liver injury and acute liver failure, and 7% of drug-induced liver injury 3.

Risk Factors and Prevention

Certain individuals are at higher risk of paracetamol toxicity, including:

• Chronic alcoholics: Who may experience liver damage even at recommended doses of paracetamol 4, 7.
• Older adults: Who may require individualized dosing due to age-related changes in liver and kidney function 7.
• Individuals with liver or kidney disease: Who may be more susceptible to the toxic effects of paracetamol 7. Prevention measures include:
• Better identification of high-risk overdoses 3.
• Improved treatment regimens, including the use of acetylcysteine as an antidote 3, 4.
• Legislative changes to restrict access to large quantities of paracetamol or modified-release formulations 3.
• Education and awareness campaigns to promote safe use of paracetamol and reduce the risk of overdose 5.